A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice

Background: The spread of SARS-CoV-2 has caused a worldwide pandemic that has affected almost every aspect of human life. The development of an effective COVID-19 vaccine could limit the morbidity and mortality caused by infection and may enable the relaxation of social-distancing measures Age is one of the most significant risk factors for poor health outcomes after SARS-CoV-2 infection there-fore, it s desirable that any new vaccine candidates elicit a robust immune response in older adults. Methods: Here, we use in-depth immunophenotyping to characterize the innate and adaptive mmune response induced upon intramusculal administration of the adennviral vectored ChAdOx1 nCoV-1 9 (AZD-1222) COVID-19 vaccine candidate in mice. Findings: A single vaccination generates spike specific Th1 cell, Th1-like Foxp3(+) regulatory T cell, polyfunctional spike-specific CD8(+) T cell and granzyme-B-producing CD8 effectors. Spike-specific IgG and IgM are generated from both the early extrafollicular antibody response and the T follicular helper co-supported germina center reaction which is associated with the production of virus-neutralizing antibodies. A single dose of this vaccine generated a similar type of immune response n aged mice hut of a reduced magnitude than in younger mice We report that a second dose enhances the mmune response to this vaccine in aged mice. Conclusions: This study shows that ChAdOx1 nCoV-19 induces both cellular and humoral immunity in adult and aged mice and suggests a prime boost strategy is a rational approach to enhance immunogenicity in older persons.